We will continue our study of the role of steroid hormones, specifically androgens such as testosterone, in the development and adult function of spinal cord regions controlling masculine copulatory behaviors. By studying a simplified model system, the spinal nucleus of the bulbocavernosus (SNB), which consists of lumbar motoneurons innervating the striated perineal muscles called bulbocavernosus (BC), we can ask fundamental questions about the role of steroid hormones in sculpting the developing nervous system and fine-tuning the adult nervous system to control behavior, especially reproductive behaviors. We will use Cre- lox- technologies in laboratory mice to selectively disable the genes for the androgen receptor (AR) and/or brain-derived neurotrophic factor (BDNF). By disabling such genes in either motoneurons or striated muscle fibers we can ask the site of androgen action for maintaining the system during perinatal development, and for regulating the somata and dendrites of the SNB motoneurons in adulthood, as well as the behavioral capacity of the system. These studies of steroidal regulation of the SNB system may prove relevant to human disorders such as amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (SBMA) and Shy Drager disease. A characteristic of each of these human disorders is that BC motoneurons are either selectively spared or selectively targeted compared to other motoneurons. Discovering how BC motoneurons are regulated by androgen may reveal why they are selectively vulnerable in human neuromuscular disorders. PUBLIC HEALTH RELEVANCE: We will continue our study of the role of steroid hormones, specifically androgens such as testosterone, in the development and adult function of spinal cord regions controlling behavior. Studying this steroid- sensitive system may afford a better understanding of human disorders such as amyotrophic lateral sclerosis, and spinal bulbar muscular atrophy, in which such steroid-sensitive motoneurons are selectively spared.